Developing an innovative patient-centred xenograft model of multiple myeloma and its use in testing novel antagonists of JAM-A signalling
Multiple myeloma (MM) is an incurable cancer in which uncontrolled plasma cell proliferation disrupts the bone marrow environment and impairs immune function. With poor 5-year patient survival (<50%), better clinical models and pipelines for targeted therapies are urgently required. This proposal will focus on both. Firstly, an MSc project will develop and validate a cutting-edge chick embryo xenograft model of MM as a robust alternative to rodent in vivo models for use in mechanistic and drug testing studies. Secondly, a PhD project will interrogate the druggability of Junctional Adhesion Molecule-A (JAM-A) signalling, recently implicated in MM progression in patients. JAM-A has not been extensively studied in MM. However it has been shown to increase in the plasma cells of MM patients with aggressive disease, and its antagonism reduces MM progression in an in vivo mouse model1 . The current proposal involves peptide antagonists of JAM-A signalling already developed by the team, which have reduced tumour progression in mouse models of breast cancer. It will make modifications to improve peptide stability and delivery, and then interrogate peptide mechanistic value in in vitro, semi-in vivo and ex vivo MM models. Finally it will use MM cell lines and MM patient-derived material in the chick xenograft model to test the utility of these novel inhibitors in translational contexts relevant to MM patients. By completion, this proposal will have delivered an innovative patientrelevant MM model ideal for testing potential new drugs; and lain the groundwork for specific JAM-A antagonists to act as lead therapeutic compounds in MM patients. The project will continue to be guided by the MM patient/patient advocate population. They have already indicated that research on novel therapies offers a huge source of hope, as MM patients consider their needs to be under-met relative to those of patients with many other cancers.
- Award Date
- 18 November 2022
- Award Value
- €262,415.00
- Principal Investigator
- Dr Ann Hopkins
- Host Institution
- RCSI
- Scheme
- HRCI-HRB Joint Funding Scheme